This proposal describes research by five NIH-funded Cornell faculty who will use 500 MHz NMR in several health-related projects. H.A. Scheraga is studying the structure, function, dynamics and folding of bovine pancreatic ribonuclease A, bovine thrombin, hirudin and epidermal growth factor to better understand their 3D structure, refolding and biological function. B. Ganem will study a genetically engineered monofunctional chorismate mutase, which has been truncated to one-third its native size while maintaining full activity. This enzyme is important in the biosynthesis of phenylalanine and tyrosine. In another project, the structures of active-site labelled polypeptides from glycosidases will be assigned. R.E. Oswald will use high resolution NMR to study protein structure and dynamics of binding of two small proteins (neuronal bungarotoxin and thymopoietin) to the nicotinic acetylcholine receptor (AChR). A complex between neuronal bungarotoxin and a peptide derived from the ACHR will be analyzed by high-field NMR. Also the structure of genetically engineered portions of the ACHR will be examined. D.B. Collum will use 6Li and 15N-NMR to probe the structures of lithiated imines, as well as the complex solution structures of lithium N,N-dialkylamides which are important reagents in modern organic chemistry. T.P. Begley will use 500 MHz NMR to elucidate the mechanism of SAM-dependent methylations and cyclopropanations by studying enzyme-substrate complexes of cyclopropane fatty acid synthase.